Alzheimer’s drug rejected for widespread use in England by NHS spending watchdog
A new Alzheimer’s drug has been rejected for widespread use in the health service in England after the health spending watchdog said it “does not currently demonstrate value for the NHS”.
The news comes as the UK’s medicines regulator said donanemab could be licensed for use in the UK.
It is the second disease-modifying Alzheimer’s drug to be rejected by the National Institute for Health and Care Excellence (Nice) in a matter of months.
One charity said the news is a “frustrating setback” for people with Alzheimer’s disease.
Alzheimer’s Research UK said the announcement “also risks signalling that the UK is no longer a good place to launch new dementia treatments”.
Donanemab, manufactured by pharmaceutical giant Eli Lilly, is a targeted antibody drug which slows the early stages of Alzheimer’s.
The drug, and another new drug for Alzheimer’s called lecanemab, have been billed as a huge step forward in research because they target a known cause of the disease, rather than just treating the symptoms.
Nice’s director of medicines evaluation, Helen Knight, said: “For Nice to be able to approve a medicine for use in the NHS it must provide additional benefits to patients, and it must also represent a good use of NHS resources and taxpayers’ money.
“Our independent committee looked at all the available evidence, including the benefits for carers. This shows donanemab could slow down cognitive decline by four to seven months, but this is just not enough benefit to justify the additional cost to the NHS. The cost-effectiveness estimate for donanemab is five to six times above what Nice normally considers an acceptable use of NHS resources.
“I know this will be disappointing news, but this is an emerging field of medicine and there are other treatments being developed.”
In August, lecanemab was approved by the medicines regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), making it the first drug of its kind to be licensed for use in the UK.
But Nice quickly said the benefits of lecanemab, made by Eisai and sold under the brand name Leqembi, are “just too small to justify the significant cost to the NHS”, and in draft guidance it said the drug should not be rolled out for widespread use across the NHS.
Concerns were raised that the decision would lead to a two-tier system for Alzheimer’s patients – with those who can afford the drug able to access it privately while others who rely on NHS care were left without.
Both donanemab and lecanemab bind to amyloid, a protein which builds up in the brains of people living with Alzheimer’s disease.
By binding to amyloid, the drugs are designed to help clear the build-up and slow down cognitive decline.
Evidence suggests people get the most benefit if they are given the treatment at an earlier stage of the disease.
Clinical trials testing the safety and efficacy of donanemab, also known as Kisunla, found it could slow the rate at which memory and thinking get worse by more than 20%.
Results also suggest the drug leads to a 40% reduction in the decline of everyday activities such as driving, enjoying hobbies and managing money.
The drug, which is given to patients in an intravenous drip once every four weeks, does carry a risk of side-effects – some of them serious, including brain swelling and micro brain bleeds.
Both donanemab and lecanemab have been approved for use in the US, though the European medicines regulator rejected lecanemab earlier this year.
Julian Beach, from the MHRA, said the drug’s safety will be kept under “close review”, adding: “Licensing medicines which meet acceptable standards of safety, quality and efficacy is a key priority for us.
“We’re assured that, together with the conditions of the licence approval, the appropriate regulatory standards for this medicine have been met.”
Hilary Evans-Newton, chief executive at Alzheimer’s Research UK, said: “Today’s announcement marks another frustrating setback for people affected by Alzheimer’s disease.
“We finally have two new treatments licensed in Britain for Alzheimer’s, but it’s incredibly disappointing that NHS patients in England and Wales won’t receive them.
“While these drugs are not cures and come with risk of side-effects, trials show they are the first treatments to slow the decline in memory and thinking skills linked to Alzheimer’s, rather than just alleviating symptoms.
“We’ve written to the Health Secretary again, calling for his leadership to bring together Nice, NHS England and industry so that people with dementia in the UK aren’t left behind.
“Today’s decision also risks signalling that the UK is no longer a good place to launch new dementia treatments.”
Professor Fiona Carragher, chief policy and research officer at Alzheimer’s Society, said: “Disease-modifying therapies like donanemab and lecanemab offer a new horizon of hope in the fight against dementia.
“MHRA’s approval of donanemab marks another milestone in this journey, but it comes alongside a draft Nice decision not to recommend donanemab for use on the NHS. While this is disheartening, we respect the decision of the regulator.”
Manufacturer Lilly welcomed the news that the drug has been licensed in the UK and said it “remains confident in the clinical and cost-effectiveness of donanemab and the value that it can bring to patients and to the NHS”.
Chris Stokes, president and general manager of UK and northern Europe at Lilly, said: “After more than 35 years of commitment to scientific progress in Alzheimer’s disease, we’re delighted that donanemab has been authorised in Great Britain for eligible adults who need effective treatment options.
“Donanemab is part of a new class of medication and has demonstrated meaningful results for people with mild cognitive impairment and mild dementia due to Alzheimer’s disease.”
Donanemab – what we know about the latest Alzheimer’s drug
What kind of treatment is Donanemab?
Donanemab is a targeted antibody drug which slows down the early stages of Alzheimer’s.
The drug, and another new drug for Alzheimer’s called lecanemab, have been billed as a huge step forward in research because they target a known cause of the disease, rather than just treating the symptoms.
Both drugs bind to amyloid, a protein which builds up in the brains of people living with Alzheimer’s disease.
By binding to amyloid, the drugs are designed to help clear the build-up and slow down cognitive decline.
How effective is it?
Manufacturer Eli Lilly found that the drug “significantly” slowed cognitive decline in Alzheimer’s patients in its clinical trials.
Donanemab, also known as Kisunla, was found to slow the rate at which memory and thinking get worse by more than 20%.
Results also suggest the drug leads to a 40% reduction in the decline of everyday activities such as driving, enjoying hobbies and managing money.
Evidence suggests that people get the most benefit if they are given the treatment earlier in the disease.
Treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, Lilly found.
How are the drugs given?
Donanemab is given to patients via an intravenous drip once every four weeks.
Lilly has said that some patients can complete their course of treatment in as little as six months once their amyloid plaque has cleared.
During the clinical trial patients were able to stop taking donanemab once they had cleared a certain amount of amyloid plaque. Around half of those involved in the trial met this threshold a year into treatment.
Are there any side effects?
Side-effects of the donanemab, and other similar drugs, can be serious.
Donanemab has been linked to “amyloid-related imaging abnormalities (Aria)” which does not usually cause symptoms but can be picked up on brain scans.
These can include temporary brain swelling or micro brain bleeds – these can be serious and even fatal in some cases.
In one clinical trial published in the Journal of the American Medical Association in 2023, 24% of people receiving donanemab had Aria.
Lilly recommends that the risk should be managed “with careful observation, monitoring with MRIs, and appropriate actions if Aria is detected”.
Three deaths were reported among the people receiving donanemab during the trial which were considered “treatment related”, according to the 2023 paper. One treatment-related death was reported in the group who receive the placebo – also known as a dummy drug.
The majority of side effects (82.4%) were either mild or were detected in tests but did not cause any symptoms.
How does a drug get approved for NHS use in the UK?
For a drug to be used in healthcare in the UK it needs to be given approval by the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA will assess the safety and efficacy of the drug before making a decision.
Before the new treatment is approved for widespread use in the health service it needs a green light from the National Institute for Health and Care Excellence (Nice) – the NHS’ spending watchdog.
The US Food and Drug Administration (FDA) approved Kisunla for the treatment of Alzheimer’s disease in July.
What happened with lecanemab?
The MHRA approved lecanemab but it was swiftly rejected by Nice.
Nice said the benefits of lecanemab are “just too small to justify the significant cost to the NHS”.
Lecanemab is already licensed in the US, where it costs about £20,000 per patient per year.
The European Medicines Agency (EMA) rejected lecanemab in late July.
It said that the drug’s effect on delaying cognitive decline “does not counterbalance the risk of serious adverse events associated with the medicine”.
But in August the regulator said that it will re-examine its opinion before issuing a final recommendation.
How much do the drugs cost?
Each vial of Kisunla is 695.65 dollars, according to Lilly documents.
The overall cost of donanemab for each person will depend on how long they are on it.
NHS England has published a briefing paper suggesting the cost of bringing new Alzheimer’s disease modifying treatments to the health service could be £500 million to £1 billion per year.
Around 50%-60% of the total estimated cost relates to the drug cost, with remaining cash spent on patient assessment, diagnosis and administering the treatment.
How do I know if I am eligible?
NHS England estimates between 50,000 and 280,000 patients might be eligible for the new treatments if they are approved for the NHS.
If the drugs are approved, patients will need to have a baseline MRI scan and then either a PET-CT scan or lumbar puncture to confirm Alzheimer’s.
It is possible that blood tests will be available in the future to diagnose the disease, so NHS England has said there should be caution about driving a “massive expansion” in other diagnostics which could become redundant in the longer term.
What have experts said?
When the stage 3 clinical trial results were reported in 2023, some experts said that the findings were “incredibly encouraging”.
Others have been cautious – with particular concerns raised about the potential side effects of the treatment.
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